MSCs engineered with secreted Klotho alleviate blood–brain barrier disruption and reduce neuroinflammation more effectively than MSCs in experimental autoimmune encephalomyelitis

• SKL-MSCs significantly outperform unmodified MSCs in reducing EAE disease severity and slowing progression. • SKL-MSCs more effectively modulate neuroinflammation by decreasing pro-inflammatory cytokines (TNF-α, IFN-γ, IL-17) and increasing anti-inflammatory IL-10. • SKL-MSCs lead to a more pronounced reduction in blood–brain barrier permeability and downregulation of BBB-associated factors (ICAM-1, VCAM-1, MMP-9, CCL2) compared to MSCs. • The enhanced therapeutic efficacy of SKL-MSCs suggests a promising strategy for treating multiple sclerosis and other neuroinflammatory conditions.